Triethylamine → 3-Hydroxymethyl-4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazine-1-carboxylic acid benzyl ester

HRID 2062239Notes

Reaction equation

HRID 2062239 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1.[CH2:20]([O:27][C:28]([N:30]1[CH2:35][CH2:34][NH:33][CH:32]([CH2:36][OH:37])[CH2:31]1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:20]([O:27][C:28]([N:30]1[CH2:35][CH2:34][N:33]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=3)[N:5]=[C:4]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[OH:19])[N:3]=2)[CH:32]([CH2:36][OH:37])[CH2:31]1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2757383Benzyl 3-(hydroxymethyl)piperazine-1-carboxylateHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 1361213213-Hydroxymethyl-4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazine-1-carboxylic acid benzyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To 2-(4-chloro-7-methyl-quinazolin-2-yl)-phenol (245 mg, 0.91 mmol) in 3.0 mL of CH2Cl2 was added sequentially 3-hydroxymethyl-piperazine-1-carboxylic acid benzyl ester (336.3 mg, 1.34 mmol) and triethylamine (190 mL, 1.37 mmol), and the reaction mixture was heated at 40° C. for 6 h. The reaction mixture was cooled and extracted with water (2×10 mL) and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure to give an oil. The residue was purified by normal phase LC (20-85% EtOAc-hexanes) to give 3-hydroxymethyl-4-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazine-1-carboxylic acid benzyl ester (216 mg, 64% yield). LC/MS: m/z 485.4 (M+H)+ at 3.02 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with water (2×10 mL)
  3. customthe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed under reduced pressure
  6. customto give an oil
  7. customThe residue was purified by normal phase LC (20-85% EtOAc-hexanes)

Sources & evidence

ORD record
ord-cd562e627bb8485ca2beb105027b9120
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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